Atopic dermatitis is known to be easily exacerbated by external stimuli such as perspiration, scratching, and friction, and the suppression or alleviation of pruritus has been the most important therapeutic goal. Atopic dermatitis is a disease with skin inflammation, rash, or eczema, and is a chronic skin disease characterized by itchiness (pruritus). While not intended to be bound by theory, it is believed that atopic dermatitis occurs when an individual with an allergic predisposition (atopic predisposition) susceptible to diseases such as bronchial asthma, allergic rhinitis, and allergic dermatitis is exposed to various stimuli. Although the mechanism of the onset of atopic dermatitis is not yet fully elucidated, it is believed to be important that Th2-associated cytokines (such as IL-4, IL-13, and IL-5) and chemical mediators (such as histamine and serotonin) be produced as a result of IgE crosslinking of Fcε receptors present on activated T cells, basophils, or mast cells, and activation caused thereby.
Therapeutic methods for atopic dermatitis that are already known include drug therapy using steroids, antihistamines, and other drugs, as well as PUVA therapy utilizing UVA (ultraviolet A) irradiation. The previous therapeutic methods, however, require taking a medicine or applying a medicine to an affected area several times every day, with the potential problem of forgetting to take or apply the medicine. Moreover, ultraviolet therapy may require a visit to the hospital as many as once or twice a week, with the potential problem of placing a burden of visiting the hospital on the patient.
Furthermore, it has been reported that the development of itchiness associated with a disease such as atopic dermatitis is not due to the release of histamine and the like only (Non Patent Literature 1). Therefore, the development of a therapeutic agent for atopic dermatitis based on a novel mechanism of action has been anticipated.
IL-31 (interleukin-31) is a T-cell cytokine. It is known that dermatitis-like symptoms similar to pruritus or atopic dermatitis occur in transgenic mice overexpressing IL-31 (Non Patent Literature 2). It has also been found that the receptor to which IL-31 binds is a heterodimer of IL-31RA (interleukin-31 receptor A) and OSMR (oncostatin M receptor) (Patent Literature 1), and IL-31 transduces signals into cells through this receptor. It has been reported that the expression of human IL-31RA is elevated in the thickened epidermis of patients with atopic dermatitis (Non Patent Literature 3).
It has previously been reported that atopic dermatitis or pruritus caused by atopic dermatitis was tried to be improved or successfully improved using an IL-31 antagonist. Moreover, IL-31 neutralizing antibodies and IL-31RA neutralizing antibodies as IL-31 antagonists have been reported (Patent Literatures 2 to 16). However, while there are reports that the expression level of IL-31 protein or RNA is increased in the serum of patients with atopic dermatitis (Non Patent Literatures 4 and 5), there is also a report that no difference in the expression level of IL-31 is observed between the skin of patients with atopic dermatitis and the skin of healthy adults (Patent Literature 8).